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Talk:Antidepressants: Difference between revisions
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'''Antidepressants''' | '''Antidepressants''' commonly refers to family of modern pharmaceutical products used in medicine for the treatment of major depressive disorder and other conditions, including dysthymia, anxiety disorders, obsessive-compulsive disorder, eating disorders, chronic pain, neuropathic pain and, in some cases, dysmenorrhoea, snoring, migraine, attention-deficit hyperactivity disorder (ADHD), dependence/addiction, and sleep disorders. They may be prescribed alone or in combination with other medications.{{citation needed}} | ||
The | The major classes of antidepressants are the [[selective serotonin reuptake inhibitor]]s ('''SSRIs'''), [[serotonin–norepinephrine reuptake inhibitors]] ('''SNRIs'''), [[MAOI|monoamine oxidase inhibitors]] ('''MAOIs'''), reversible monoamine oxidase A inhibitors ('''rMAO-A inhibitors'''), tetracyclic antidepressants ('''TeCAs'''), and noradrenergic and specific serotonergic antidepressant ('''NaSSAs'''). Herbal substances such as '''St. John's wort''' is also sometimes used in the treatment of depression<ref>Linde, K., Kriston, L., Rucker, G., Jamil, S., Schumann, I., Meissner, K., . . . Schneider, A. (2015). '''''Efficacy and Acceptability of Pharmacological Treatments for Depressive Disorders in Primary Care: Systematic Review and Network Meta-Analysis.''''' ''The Annals of Family Medicine'', 13(1), 69-79. doi:10.1370/afm.1687</ref><ref>Linde, K., Berner, M. M., & Kriston, L. (2008). St John's wort for major depression. ''Cochrane Database of Systematic Reviews''. doi:10.1002/14651858.cd000448.pub3</ref> | ||
== Major Types == | |||
* [[Selective serotonin reuptake inhibitor]]s ('''SSRIs''') | |||
* [[Serotonin–norepinephrine reuptake inhibitor]]s ('''SNRIs''') | |||
* Reversible monoamine oxidase A inhibitors ('''rMAO-AI''') | |||
* Monoamine oxidase inhibitors ('''MAOIs''') | |||
* Tetracyclic antidepressants ('''TeCAs''') | |||
== Pharmacology == | == Pharmacology == | ||
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The earliest and probably most widely accepted scientific theory of antidepressant action is the monoamine hypothesis (which can be traced back to the 1950s), which states that depression is due to an imbalance (most often a deficiency) of the [[monoamine neurotransmitter]]s (namely [[serotonin]], [[norepinephrine]] and [[dopamine]]).<ref name = GG /> It was originally proposed based on the observation that certain hydrazine anti-tuberculosis agents produce antidepressant effects, which was later linked to their inhibitory effects on [[monoamine oxidase]], the enzyme that catalyses the breakdown of the monoamine neurotransmitters.<ref name = GG /> All currently marketed antidepressants have the monoamine hypothesis as their theoretical basis, with the possible exception of agomelatine which acts on a dual [[Melatonin|melatonergic]]-[[Serotonin|serotonergic]] pathway.<ref name = GG /> Despite the success of the monoamine hypothesis it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, there are a sizeable portion (>40%) of depressed patients that do not adequately respond to monoaminergic antidepressants.<ref name="Infl">{{cite journal |vauthors=Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M | title = The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression | journal = Metabolic Brain Disease | volume = 24 | issue = 1 | pages = 27–53 | date = March 2009 | pmid = 19085093 | doi = 10.1007/s11011-008-9118-1 }}</ref><ref name="glut">{{cite journal |vauthors=Sanacora G, Treccani G, Popoli M | title = Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders | journal = Neuropharmacology | volume = 62 | issue = 1 | pages = 63–77 | date = January 2012 | pmid = 21827775 | doi = 10.1016/j.neuropharm.2011.07.036 | pmc=3205453}}</ref> A number of alternative hypotheses have been proposed, including the glutamate, neurogenic, [[Epigenetics|epigenetic]], cortisol hypersecretion and inflammatory hypotheses.<ref name = Infl /><ref name = glut /><ref name="Epig">{{cite journal |vauthors=Menke A, Klengel T, Binder EB | title = Epigenetics, depression and antidepressant treatment | journal = Current Pharmaceutical Design | volume = 18 | issue = 36 | pages = 5879–5889 | year = 2012 | pmid = 22681167 | doi = 10.2174/138161212803523590 }}</ref><ref name="Epig2">{{cite journal |vauthors=Vialou V, Feng J, Robison AJ, Nestler EJ | title = Epigenetic mechanisms of depression and antidepressant action | journal = Annual Review of Pharmacology and Toxicology | volume = 53 | issue = 1 | pages = 59–87 | date = January 2013 | pmid = 23020296 | doi = 10.1146/annurev-pharmtox-010611-134540 }}</ref> | The earliest and probably most widely accepted scientific theory of antidepressant action is the monoamine hypothesis (which can be traced back to the 1950s), which states that depression is due to an imbalance (most often a deficiency) of the [[monoamine neurotransmitter]]s (namely [[serotonin]], [[norepinephrine]] and [[dopamine]]).<ref name = GG /> It was originally proposed based on the observation that certain hydrazine anti-tuberculosis agents produce antidepressant effects, which was later linked to their inhibitory effects on [[monoamine oxidase]], the enzyme that catalyses the breakdown of the monoamine neurotransmitters.<ref name = GG /> All currently marketed antidepressants have the monoamine hypothesis as their theoretical basis, with the possible exception of agomelatine which acts on a dual [[Melatonin|melatonergic]]-[[Serotonin|serotonergic]] pathway.<ref name = GG /> Despite the success of the monoamine hypothesis it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, there are a sizeable portion (>40%) of depressed patients that do not adequately respond to monoaminergic antidepressants.<ref name="Infl">{{cite journal |vauthors=Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M | title = The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression | journal = Metabolic Brain Disease | volume = 24 | issue = 1 | pages = 27–53 | date = March 2009 | pmid = 19085093 | doi = 10.1007/s11011-008-9118-1 }}</ref><ref name="glut">{{cite journal |vauthors=Sanacora G, Treccani G, Popoli M | title = Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders | journal = Neuropharmacology | volume = 62 | issue = 1 | pages = 63–77 | date = January 2012 | pmid = 21827775 | doi = 10.1016/j.neuropharm.2011.07.036 | pmc=3205453}}</ref> A number of alternative hypotheses have been proposed, including the glutamate, neurogenic, [[Epigenetics|epigenetic]], cortisol hypersecretion and inflammatory hypotheses.<ref name = Infl /><ref name = glut /><ref name="Epig">{{cite journal |vauthors=Menke A, Klengel T, Binder EB | title = Epigenetics, depression and antidepressant treatment | journal = Current Pharmaceutical Design | volume = 18 | issue = 36 | pages = 5879–5889 | year = 2012 | pmid = 22681167 | doi = 10.2174/138161212803523590 }}</ref><ref name="Epig2">{{cite journal |vauthors=Vialou V, Feng J, Robison AJ, Nestler EJ | title = Epigenetic mechanisms of depression and antidepressant action | journal = Annual Review of Pharmacology and Toxicology | volume = 53 | issue = 1 | pages = 59–87 | date = January 2013 | pmid = 23020296 | doi = 10.1146/annurev-pharmtox-010611-134540 }}</ref> | ||
== Clinical Guidelines == | == Clinical Guidelines for Diagnosis and Prescription == | ||
=== Major Depressive Disorder === | === Major Depressive Disorder === | ||
The UK [https://en.wikipedia.org/wiki/National_Institute_for_Health_and_Care_Excellence National Institute for Health and Care Excellence( NICE)] 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression because the risk-benefit ratio is poor. The guidelines recommend that antidepressant treatment should be considered for: | The UK [https://en.wikipedia.org/wiki/National_Institute_for_Health_and_Care_Excellence National Institute for Health and Care Excellence( NICE)] 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression because the risk-benefit ratio is poor. The guidelines recommend that antidepressant treatment should be considered for: | ||
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=== General === | === General === | ||
Almost any medication involved with serotonin regulation has the potential to cause [[serotonin syndrome|serotonin toxicity]] (also known as ''serotonin syndrome''){{spaced ndash}} an excess of serotonin that can induce mania, restlessness, agitation, [[emotional lability]], insomnia and confusion as its primary symptoms.<ref name="pmid12771076">{{cite journal |vauthors=Birmes P, Coppin D, Schmitt L, Lauque D | title = Serotonin syndrome: a brief review | journal = CMAJ | volume = 168 | issue = 11 | pages = 1439–42 | year = 2003 | pmid = 12771076 | pmc = 155963 | doi = }}</ref><ref name="pmid15784664">{{cite journal |vauthors=Boyer EW, Shannon M | title = The serotonin syndrome | journal = N. Engl. J. Med. | volume = 352 | issue = 11 | pages = 1112–20 | year = 2005 | pmid = 15784664 | doi = 10.1056/NEJMra041867 | url = http://toxicology.ucsd.edu/art%203%20serotonin%20syndrome.pdf | format = PDF | archiveurl = https://web.archive.org/web/20130618053344/http://toxicology.ucsd.edu/art%203%20serotonin%20syndrome.pdf | archivedate = 18 June 2013 }}</ref> Although the condition is serious, it is not particularly common, generally only appearing at high doses or while on other medications. Assuming proper medical intervention has been taken (within about 24 hours) it is rarely fatal.<ref name="pmid10941349">{{cite journal |vauthors=Mason PJ, Morris VA, Balcezak TJ | title = Serotonin syndrome. Presentation of 2 cases and review of the literature | journal = Medicine | volume = 79 | issue = 4 | pages = 201–9 | year = 2000 | pmid = 10941349 | doi = 10.1097/00005792-200007000-00001 }}</ref><ref name="pmid10818648">{{cite journal |vauthors=Sampson E, Warner JP | title = Serotonin syndrome: potentially fatal but difficult to recognize | journal = Br J Gen Pract | volume = 49 | issue = 448 | pages = 867–8 | year = 1999 | pmid = 10818648 | pmc = 1313553 | doi = }}</ref> | Almost any medication involved with serotonin regulation has the potential to cause [[serotonin syndrome|serotonin toxicity]] (also known as ''serotonin syndrome''){{spaced ndash}} an excess of serotonin that can induce mania, restlessness, agitation, [[emotional lability]], insomnia and confusion as its primary symptoms.<ref name="pmid12771076">{{cite journal |vauthors=Birmes P, Coppin D, Schmitt L, Lauque D | title = Serotonin syndrome: a brief review | journal = CMAJ | volume = 168 | issue = 11 | pages = 1439–42 | year = 2003 | pmid = 12771076 | pmc = 155963 | doi = }}</ref><ref name="pmid15784664">{{cite journal |vauthors=Boyer EW, Shannon M | title = The serotonin syndrome | journal = N. Engl. J. Med. | volume = 352 | issue = 11 | pages = 1112–20 | year = 2005 | pmid = 15784664 | doi = 10.1056/NEJMra041867 | url = http://toxicology.ucsd.edu/art%203%20serotonin%20syndrome.pdf | format = PDF | archiveurl = https://web.archive.org/web/20130618053344/http://toxicology.ucsd.edu/art%203%20serotonin%20syndrome.pdf | archivedate = 18 June 2013 }}</ref> Although the condition is serious, it is not particularly common, generally only appearing at high doses or while on other medications. Assuming proper medical intervention has been taken (within about 24 hours) it is rarely fatal.<ref name="pmid10941349">{{cite journal |vauthors=Mason PJ, Morris VA, Balcezak TJ | title = Serotonin syndrome. Presentation of 2 cases and review of the literature | journal = Medicine | volume = 79 | issue = 4 | pages = 201–9 | year = 2000 | pmid = 10941349 | doi = 10.1097/00005792-200007000-00001 }}</ref><ref name="pmid10818648">{{cite journal |vauthors=Sampson E, Warner JP | title = Serotonin syndrome: potentially fatal but difficult to recognize | journal = Br J Gen Pract | volume = 49 | issue = 448 | pages = 867–8 | year = 1999 | pmid = 10818648 | pmc = 1313553 | doi = }}</ref> | ||
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With the explosion of use and interest in SSRIs in the late 1980s and early 1990s, focused especially on [[Prozac#Popular culture|Prozac]], interest grew as well in discontinuation syndromes.<ref>{{cite news |url=https://www.nytimes.com/2007/05/06/magazine/06antidepressant-t.html|work=New York Times |title=Self-Nonmedication |first=Bruce |last=Stutz |date=6 May 2007 |accessdate=24 May 2010}}</ref> In the late 1990s, some investigators thought that symptoms that emerged when antidepressants were discontinued, might mean that antidepressants were causing [[addiction]], and some used the term "withdrawal syndrome" to describe the symptoms. Addictive substances cause [[physiological dependence]], so that [[drug withdrawal]] causes suffering. These theories were abandoned, since addiction leads to [[drug-seeking behavior]], and people taking antidepressants do not exhibit drug-seeking behavior. The term "withdrawal syndrome" is no longer used with respect to antidepressants, to avoid confusion with problems that arise from addiction.<ref name="WarnerAFP" /><ref>{{cite journal | author = Shelton RC | year = 2006 | title = The nature of the discontinuation syndrome associated with antidepressant drugs | url = | journal = J Clin Psychiatry | volume = 67 | issue = Suppl 4| pages = 3–7 | pmid = 16683856 }}</ref><ref>WHO (2003) [http://apps.who.int/medicinedocs/fr/d/Js4896e/9.html WHO Expert Committee on Drug Dependence – WHO Technical Report Series, No. 915 – Thirty-third Report]</ref> There are case reports of antidepressants being abused, but these are rare and are mostly limited to antidepressants with stimulant effects and to people who already had a substance use disorder.<ref>{{cite journal |vauthors=Evans EA, Sullivan MA | date = Aug 2014 | title = Abuse and misuse of antidepressants | url = | journal = Subst Abuse Rehabil | volume = 5 | issue = | pages = 107–20 | doi = 10.2147/SAR.S37917 | pmid = 25187753 }}</ref> A 2012 comparison of the effects of stopping therapy with [[benzodiazepine]]s and [[SSRI]]s argued that because the symptoms are similar, it makes no sense to say that benzodiazepines are addictive while SSRIs are not.<ref>{{cite journal |vauthors=Nielsen M, et al. | date = May 2012 | title = What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors | url = | journal = Addiction | volume = 107 | issue = 5| pages = 900–8 | doi = 10.1111/j.1360-0443.2011.03686.x | pmid = 21992148 }}</ref> Responses to that review noted that there is no evidence that people who stop taking SSRIs exhibit drug-seeking behavior while people who stop taking benzodiazepines do, and that the drug classes should be considered differently.<ref>{{cite journal | author = Brady K | date = May 2012 | title = Withdrawal or dependence: a matter of context. Comment on: What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors | url = | journal = Addiction | volume = 107 | issue = 5| pages = 910–1 | doi = 10.1111/j.1360-0443.2012.03862.x | pmid = 22471576 }}</ref><ref>{{cite journal | author = Lader M | date = May 2012 | title = Dependence and withdrawal: comparison of the benzodiazepines and selective serotonin re-uptake inhibitors. Comment on: What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors | url = | journal = Addiction | volume = 107 | issue = 5| pages = 909–10 | doi = 10.1111/j.1360-0443.2011.03736.x | pmid = 22471575 }}</ref> | With the explosion of use and interest in SSRIs in the late 1980s and early 1990s, focused especially on [[Prozac#Popular culture|Prozac]], interest grew as well in discontinuation syndromes.<ref>{{cite news |url=https://www.nytimes.com/2007/05/06/magazine/06antidepressant-t.html|work=New York Times |title=Self-Nonmedication |first=Bruce |last=Stutz |date=6 May 2007 |accessdate=24 May 2010}}</ref> In the late 1990s, some investigators thought that symptoms that emerged when antidepressants were discontinued, might mean that antidepressants were causing [[addiction]], and some used the term "withdrawal syndrome" to describe the symptoms. Addictive substances cause [[physiological dependence]], so that [[drug withdrawal]] causes suffering. These theories were abandoned, since addiction leads to [[drug-seeking behavior]], and people taking antidepressants do not exhibit drug-seeking behavior. The term "withdrawal syndrome" is no longer used with respect to antidepressants, to avoid confusion with problems that arise from addiction.<ref name="WarnerAFP" /><ref>{{cite journal | author = Shelton RC | year = 2006 | title = The nature of the discontinuation syndrome associated with antidepressant drugs | url = | journal = J Clin Psychiatry | volume = 67 | issue = Suppl 4| pages = 3–7 | pmid = 16683856 }}</ref><ref>WHO (2003) [http://apps.who.int/medicinedocs/fr/d/Js4896e/9.html WHO Expert Committee on Drug Dependence – WHO Technical Report Series, No. 915 – Thirty-third Report]</ref> There are case reports of antidepressants being abused, but these are rare and are mostly limited to antidepressants with stimulant effects and to people who already had a substance use disorder.<ref>{{cite journal |vauthors=Evans EA, Sullivan MA | date = Aug 2014 | title = Abuse and misuse of antidepressants | url = | journal = Subst Abuse Rehabil | volume = 5 | issue = | pages = 107–20 | doi = 10.2147/SAR.S37917 | pmid = 25187753 }}</ref> A 2012 comparison of the effects of stopping therapy with [[benzodiazepine]]s and [[SSRI]]s argued that because the symptoms are similar, it makes no sense to say that benzodiazepines are addictive while SSRIs are not.<ref>{{cite journal |vauthors=Nielsen M, et al. | date = May 2012 | title = What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors | url = | journal = Addiction | volume = 107 | issue = 5| pages = 900–8 | doi = 10.1111/j.1360-0443.2011.03686.x | pmid = 21992148 }}</ref> Responses to that review noted that there is no evidence that people who stop taking SSRIs exhibit drug-seeking behavior while people who stop taking benzodiazepines do, and that the drug classes should be considered differently.<ref>{{cite journal | author = Brady K | date = May 2012 | title = Withdrawal or dependence: a matter of context. Comment on: What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors | url = | journal = Addiction | volume = 107 | issue = 5| pages = 910–1 | doi = 10.1111/j.1360-0443.2012.03862.x | pmid = 22471576 }}</ref><ref>{{cite journal | author = Lader M | date = May 2012 | title = Dependence and withdrawal: comparison of the benzodiazepines and selective serotonin re-uptake inhibitors. Comment on: What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors | url = | journal = Addiction | volume = 107 | issue = 5| pages = 909–10 | doi = 10.1111/j.1360-0443.2011.03736.x | pmid = 22471575 }}</ref> | ||
==History of development== | ==History of development== | ||